Adult periodontitis has been conceptualized as a chronic inflammatory disease. It is initiated by the accumulation of bacterial plaque within the gingival sulcus. The host response to these microbial antigens diminishes the number of these organisms, but simultaneOusly causes extensive destruction of the collagenous connective tissue matrix, as well as loss of the supporting alveolar bone. Besides microbial antigens, evidence is mounting which supports the concept that some endogenous antigens may function in a pathogenic role. Studies have documented elevated levels of immunoglobulin directed against various host proteins in inflamed gingival tissue. These include antibodies directed against aggregated IgG, double stranded DNA, desmosomal antigens, as well as types l and 111 collagen. Thus, high levels of antibody targeted against various host components in inflamed gingival tissue suggest an interplay between periodontal infection and autoimmunity. There is a particular B lymphocyte lineage (CD5/LY1/B1) which has a propensity for secreting high levels of autoantibody. Interestingly, augmented numbers of these B cells have been detected within inflamed gingival tissue. A particular cytokine, interleukin 10 (IL-10), has been reported to selectively favor the development of this B cell lineage. Therefore, the objective of this proposal is to determine whether IL-10 is elevated in inflamed gingival tissue and if it can potentiate the production of anti- collagen antibodies by these CD5 positive B cells. Our preliminary results demonstrate that gingival mononuclear cells extracted from adult periodontitis patients constitutively produce IL-I 0, and treatment with IL-I 0 potentiates anti-collagen antibody production. Hence, we will investigate whether IL-I 0 plays an important role in promoting the expansion of CD5 positive B cells, and if IL-I 0 enhances the production of IgG anti-collagen antibodies by this B lymphocyte lineage. This proposal will help to define the role which the autoimmune response plays in the pathogenesis of adult periodontitis.